LGALS1 belongs to the family of animal lectins, which are highly conserved throughout evolution. Galectins share remarkable sequence similarities in the carbohydrate recognition domain and have affinity for polylactosamine-enriched glycoconjugates (1, 2). LGALS1 encodes a β-galactoside binding protein (β-GBP) and is known to bind to leukocyte membrane antigens like CD45, CD43, and CD7 (3-5). The protein can occur both as a monomer (˜14.5 kDa, β-GBP) and a homodimer (˜29 kDa, galectin-1) (2, 6). In its monomeric form, β-GBP inhibits T cell proliferation by arresting cells in the S and G2/M phases (7). As a homodimer, galectin-1 has various effects on cell-cell and cell-matrix interactions (8, 9). By crosslinking of T-cell surface proteins, galectin-1 induces apoptosis of activated but not resting T-cells (10). This process is mediated by activation of transcription factors NFAT and AP-1 and by downregulation of Bcl-2 protein (11, 12). Susceptibility of immature thymocytes to galectin-1 induced apoptosis suggests a role for the protein during thymic selection (13).
One of the most intriguing functions of the galectin-1 protein is its role in immunomodulation. Research over the past decades has identified a beneficial role for galectin-1 in several models of autoimmune diseases (14-16). Recently, it was demonstrated that galectin-1 inhibits the allogeneic T cell response in a dose- and carbohydrate dependent way. Downregulation of the immune response appeared to involve both apoptosis of activated T cells and non-apoptotic mechanisms (17). Galectin-1 can play a role in downregulation of the immune response by modulating cytokine production. In a mouse model for rheumatoid arthritis, treatment with galectin-1 protein resulted in a shift from a T helper 1 (TH1) toward a T helper 2 (TH2) type response, which was accompanied by downregulation of interferon (IFN)-γ and upregulation of interleukin (IL)-5 in draining lymph nodes (16). Furthermore, galectin-1 treatment induced a reduction of IFN-γ and tumor necrosis factor (TNF)-α production in con-A induced hepatitis in mice (18) and in IL-2 activated T cells (9). Recently, it was described that galectin-1 also suppresses experimental colitis in mice (19). In this model, a decrease in inflammatory cytokine production was observed, together with apoptosis of mononuclear cells.